The evaluation and optimal use of rituximab in lymphoid malignancies

Abstract

Rituximab is an IgG1, chimeric monoclonal antibody (mAb) containing murine light-and heavy-chain variable-region sequences and human constant-region sequences. Rituximab targets the CD20 molecule expressed on normal and malignant B-lymphocytes. At present, rituximab is the most important mAb of clinical value in patients with B-cell lymphoid malignancies. Since approval in 1997, rituximab has become widely used in chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and diffused large B-cell lymphoma (DLBCL) when combined with chemotherapy. Currently, rituximab is commonly combined with first-line chemotherapy for FL and should be offered as maintenance therapy to all appropriate patients with this disease. Randomized Phase III trials demonstrated the superiority of rituximab added to CHOP chemotherapy against CHOP chemotherapy alone in patients with DLBCL. Rituximab alone has limited activity in MCL but can be used in MCL in combination with chemotherapy, despite the benefits not being as impressive as when used against other lymphoma entities. In addition, for the less frequent B-cell lymphomas, small series show considerable activity for most of these entities. Fludarabine and rituximab combination therapies in CLL yielded promising results in several studies. Two large Phase III randomized trials demonstrated the superiority of chemoimmunotherapy with rituximab compared with chemotherapy alone in previously untreated and refractory/relapsed patients with CLL. Therefore, it can be concluded that rituximab, with only few exceptions, can generally be accepted as a standard component of anti B-cell non-Hodgkin's lymphoma therapies. In this review, the pharmacology, mode of action, pharmacokinetics, and current place in the therapy of B-cell lymphoid malignancies of rituximab are presented. In addition, an overview of studies conducted to date and optimal use of this drug, including timing and doses, is presented.

Targeted drug delivery for cancer therapy: the other side of antibodies

“…First, we present an overview of the biological aspects of FDA approved TMAs, particularly those used for hematological cancers. (For summaries of the clinical efficacies of these drugs the reader is referred to recent reviews [6-8]). Similarly, we then discuss ADCs, highlighting their potential advantages.…”